1. Field of the Invention
The present invention relates generally to apparatus and methods for inhibiting restenosis in blood vessels following angioplasty or other intravascular procedures for treating atherosclerosis and other diseases of the vasculature. More particularly, the present invention provides improved apparatus and methods for cryogenically treating a lesion within a patient""s vasculature to inhibit hyperplasia (which often occurs after intravascular procedures).
A number of percutaneous intravascular procedures have been developed for treating atherosclerotic disease in a patient""s vasculature. The most successful of these treatments is percutaneous transluminal angioplasty (PTA). PTA employs a catheter having an expansible distal end, usually in the form of an inflatable balloon, to dilate a stenotic region in the vasculature to restore adequate blood flow beyond the stenosis. Other procedures for opening stenotic regions include directional arthrectomy, rotational arthrectomy, laser angioplasty, stents and the like. While these procedures, particularly PTA and stenting, have gained wide acceptance, they continue to suffer from the subsequent occurrence of restenosis.
Restenosis refers to the re-narrowing of an artery following an initially successful angioplasty or other primary treatment. Restenosis typically occurs within weeks or months of the primary procedure, and may affect up to 50% of all angioplasty patients to some extent. Restenosis results at least in part from smooth muscle cell proliferation in response to the injury caused by the primary treatment. This cell proliferation is referred to as xe2x80x9chyperplasia.xe2x80x9d Blood vessels in which significant restenosis occurs will typically require further treatment.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation, the administration of anti-thrombotic drugs following the primary treatment, stenting of the region following the primary treatment, and the like. While these proposals have enjoyed varying levels of success, no one of these procedures is proven to be entirely successful in avoiding all occurrences of restenosis and hyperplasia.
It has recently been proposed to prevent or slow reclosure of a lesion following angioplasty by remodeling the lesion using a combination of dilation and cryogenic cooling. Co-pending U.S. patent application Ser. No. 09/203,011, filed Dec. 1, 1998 (Attorney Docket No. 18468-000110), the full disclosure of which is incorporated herein by reference, describes an exemplary structure and method for inhibiting restenosis using a cryogenically cooled balloon. While these proposals show great promise for endovascular use, the described structures and methods for carrying out endovascular cryogenic cooling would benefit from still further improvements. In particular, it can be challenging to safely and reproducibly effect the desired controlled cooling. For example, many potential cryogenic fluids, such as liquid nitrous oxide, exhibit high levels of heat transfer. This is problematic as high cooling temperatures may kill the cooled cells (cell necrosis) rather than provoking the desired antiproliferative effect of endoluminal cryotherapy. Additionally, the use of nitrous oxide as a balloon inflation media often results in limited visibility of the cooling balloon, especially smaller sized balloons, making it difficult to properly visualize the inflated cooling balloon within a lesion site. Further, improved safety measures that would prevent against cooling balloon failures and/or minimize leakage of any cryogenic fluids into the blood stream would be beneficial. Moreover, cryogenic systems having low profiles and enhanced performance characteristics would be advantageous.
For these reasons, it would be desirable to provide improved devices, systems, and methods for treatment of restenosis and hyperplasia in blood vessels. It would be particularly desirable if these improved devices, systems, and methods were capable of delivering treatment in a very controlled and safe manner so as to avoid overcooling and/or injury to adjacent tissue. These devices, systems, and methods should ideally also inhibit hyperplasia and/or neoplasia in the target tissue with minimum side effects. At least some of these objectives will be met by the invention described herein.
2. Description of the Background Art
A cryoplasty device and method are described in WO 98/38934. Balloon catheters for intravascular cooling or heating a patient are described in U.S. Pat. No. 5,486,208 and WO 91/05528. A cryosurgical probe with an inflatable bladder for performing intrauterine ablation is described in U.S. Pat. No. 5,501,681. Cryosurgical probes relying on Joule-Thomson cooling are described in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713; and 3,901,241. Catheters with heated balloons for post-angioplasty and other treatments are described in U.S. Pat. Nos. 5,196,024; 5,191,883; 5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752. Cryogenic fluid sources are described in U.S. Pat. Nos. 5,644,502; 5,617,739; and 4,336,691. A body cooling apparatus is described in U.S. Pat. No. 3,125,096. Rapid exchange catheters are described in U.S. Pat. Nos. 5,383,853 and 5,667,521. The following U.S. patents may also be relevant to the present invention: U.S. Pat. Nos. 5,458,612; 5,545,195; and 5,733,280.
The fall disclosures of each of the above references are incorporated herein by reference.
The present invention provides improved devices, system, and methods for inhibiting hyperplasia in blood vessels. The blood vessels will often be treated for atherosclerotic or other diseases by balloon angioplasty, arthrectomy, rotational arthrectomy, laser angioplasty, stenting, or another primary treatment procedure. Inhibition of excessive cell growth is desirable when such treatments are employed so as to reduce and/or eliminate any associated hyperplasia and to maintain the patency of a body lumen. The present invention allows for cryotherapy treatment of a target portion within the body lumen of a patient in a very controlled and safe manner, particularly when using fluid capable of cooling tissues below a target temperature range.
In a first aspect, the invention provides a cryotherapy catheter comprising a catheter body having a proximal end and a distal end with a cooling fluid supply lumen and an exhaust lumen extending therebetween. A first balloon is disposed near the distal end of the catheter body in fluid communication with the supply and exhaust lumens. A second balloon is disposed over the first balloon with a barrier, typically a thermal barrier, therebetween.
Treatment according to this first aspect of the present invention can be effected by positioning the first balloon within the blood vessel adjacent a target portion. The xe2x80x9ctarget portionxe2x80x9d will often be a length within the blood vessel which is at risk of hyperplasia, typically as a result of balloon angioplasty (or some other treatment). Cryogenic cooling fluid is introduced into the first balloon (in which it often vaporizes) and exhausted. The second balloon expands to radially engage the vessel wall. The target portion is cooled to a temperature which is sufficiently low for a time which is sufficiently long to inhibit excessive cell proliferation. Heat transfer will be inhibited between the first and second balloons by the thermal barrier so as to limit cooling of the target portion. The inhibited cooling treatment will be directed at all or a portion of a circumferential surface of the body lumen, and will preferably result in cell growth inhibition, but not necessarily in significant cell necrosis. Particularly in the treatment of arteries before, during, and/or following balloon angioplasty, cell necrosis may be undesirable if it increases the hyperplastic response. Thus, the present invention will cool target tissue to a limited cooling temperatures to slow or stop cell proliferation.
In some embodiments, the barrier may comprise a separation or gap maintained between the balloons by a polyester layer. The polyester layer typically comprises a woven, braided, helically wound, or knotted polyester material. The polyester layer may be puncture resistant so as to provide further protection against any leakage of fluid from the first balloon. The polyester material may additionally help retain balloon folds of the first and/or second balloons after they are expanded so that the balloons may be more easily drawn back after a treatment procedure. The barrier may alternatively comprise a separation maintained between the balloons by a fluid layer. The fluid layer may comprise at least one liquid selected from the group consisting of propylene glycol, propylene glycol 200, propylene glycol 300, propylene glycol 400, propylene glycol 600, glycerin, ethyl alcohol 75%, ethyl alcohol 95%, dimethyl sulfoxide, glyceryl formal, N-methyl-2-pyrrolidose, tetrahydrofurfuryl, dimethyl acetamide, and monthiol glycerol.
A radiopaque marker may be disposed on or within the barrier for proper positioning of the cryotherapy balloons within the target portion of the blood vessel under fluoroscopy. For example, the radiopaque marker may be disposed on the polyester layer in a stent-like pattern or radiopaque contrast agent may be disposed within the fluid layer. The radiopaque marker is preferably a non-toxic contrast medium, such as, gold, and preferably tungsten and does not significantly alter the thermal insulation properties of the barrier. Areas of the barrier adjacent the balloon folds may be free of any radiopaque marking so as to further minimize the balloon profile. The radiopaque marker may also be electrically conductive so as to monitor any leaks in the separation between the balloons or to measure an interface temperature between the balloons.
Suitable cryogenic fluids will preferably be non-toxic and include liquid nitrous oxide, liquid carbon dioxide, cooled saline and the like. The balloons are preferably inelastic and have a length of at least 1 cm each, more preferably in the range from 2 cm to 5 cm each in a coronary artery and 2 cm to 10 cm each in a periphery artery. The balloons will have diameters in the range from 2 mm to 5 mm each in a coronary artery and 2 mm to 10 mm each in a periphery artery. Generally, the temperature of the outer surface of the first balloon will be in a range from about 0xc2x0 C. to about xe2x88x9250xc2x0 C. and the temperature of the outer surface of the second balloon will be in a range from about xe2x88x923xc2x0 C. to about xe2x88x9215xc2x0 C. This will provide a treatment temperature in a range from about xe2x88x923xc2x0 C. to about xe2x88x9215xc2x0 C. The tissue is typically maintained at the desired temperature for a time period in the range from about 1 to 60 seconds, preferably being from 20 to 40 seconds. Hyperplasia inhibiting efficacy may be enhanced by repeating cooling in cycles, typically with from about 1 to 3 cycles, with the cycles being repeated at a rate of about one cycle every 60 seconds.
In another aspect of the present invention, a cryotherapy system comprises an elongate body having a proximal end and a distal end with a fluid supply, an exhaust lumen, and a plurality of vacuum lumens extending therebetween. A first balloon defines a volume in fluid communication with the supply and exhaust lumens. A fluid shutoff couples a cryogenic fluid supply with the supply lumen. A second balloon is disposed over the first balloon with a vacuum space therebetween. The vacuum space is coupled to the fluid shutoff by the plurality of vacuum lumens. The fluid shutoff inhibits flow of cryogenic fluid into the first balloon in response to a change in at least one of the vacuum lumens and/or in response to a change in the vacuum space. Advantageously, the cryotherapy system can monitor the integrity of both the catheter body and the balloons during cooling to ensure that there are no breaches in the catheter shaft or the balloons. Further, in the event of a failure, the fluid shutoff can prevent the delivery of additional cryogenic fluid into the supply lumen and the second balloon can act to contain any cryogenic fluid that may have escaped the first balloon.
The fluid shutoff typically comprises a vacuum switch connected to a shutoff valve by a circuit, the circuit being powered by a battery. The switch may remain closed only when a predetermined level of vacuum is detected. The closed switch allows the shutoff valve (in fluid communication with the cryogenic fluid supply) to be open. Alternatively, the circuit may be arranged so that the switch is open only when the predetermined vacuum is present, with the shutoff valve being open when the switch is open. The vacuum is reduced when there is a breach in the catheter body, allowing cryogenic fluid or blood to enter at least one vacuum lumen, the first balloon is punctured, allowing cryogenic fluid to enter the vacuum space, or the second balloon is punctured, allowing blood to enter the vacuum space. The vacuum may be provided by a positive displacement pump, such as a syringe, coupled to the vacuum space by the plurality of vacuum lumens. A valve, such as a stopcock, may be disposed between the syringe and the vacuum lumens so as to isolate a relatively large syringe volume from a relatively small vacuum volume. This in turn allows for increased sensitivity of small fluid leaks as the detection of changes in the vacuum as small as 0.2 mL may be monitored.
The system may further comprise a hypsometer with a thermocouple, pressure transducer, capillary tube, thermistor, or the like, coupled to the first balloon to determine a temperature and/or pressure of fluid in the first balloon. An indicator, such as a warning light or audio signal, may additionally be coupled to the thermocouple to provide a signal to an operator of the system when the first balloon temperature is above 0xc2x0 C. As cryoplasty often results in adhesion of the cooling balloon to the vessel wall during treatment, an indicator allows an operator to know when to safely remove the cooling balloon at a safe temperature following treatment so that any potential tearing of the vessel resulting from a frozen cooling balloon is minimized.
In yet another aspect, the present invention provides a cryotherapy catheter comprising a catheter body having a proximal end and distal end with a cooling fluid supply lumen and an exhaust lumen extending therebetween. A first balloon is disposed at the distal end of the catheter body, the first balloon having an inner surface in fluid communication with the supply and exhaust lumens. A second balloon is disposed over the first balloon, wherein proximal and distal balloon stems of the first and second balloon are staggered along the distal end of the catheter body. The balloons stems or bond joints are staggered to provide a lower balloon folding profile and to allow positioning of a vacuum port between the proximal balloon stems of the first and second balloons. The balloon stems of the first and second balloons will be staggered from each other by a distance of 5 mm or less, preferably from about 2 mm to about 3 mm. The cryotherapy catheter may further comprise at least one rupture disk molded into a proximal or distal balloon stem of the first balloon. In some instances, cryotherapy balloons may fail or burst on inner bond joints in a peel mode. As such, it is desirable to mold rupture discs into the balloons stems to preclude such bond joint failures. Rupture discs will reduce a stem thickness to about 0.0005 inches or less.
In another aspect of the present invention, a cryotherapy system comprises a catheter body having a proximal end and a distal end with a cooling fluid supply lumen and an exhaust lumen extending therebetween. A balloon is disposed at the distal end of the catheter body, the first balloon having an inner surface in fluid communication with the supply lumen and exhaust lumen. A pressure transducer is coupled to the catheter body so as to measure gas pulse pressure therein. A fluid shutoff couples a cryogenic cooling fluid supply with the supply lumen. The pressure transducer is coupled to the fluid shutoff so as to inhibit flow of cryogenic fluid into the first balloon if the pressure measured by the pressure transducer is below 60 psi or above 80 psi. Alternatively, the fluid shutoff may inhibit flow of cryogenic fluid into the first balloon if a pressure decay measured by the pressure transducer is greater than 5 psi. Hence, the present system incorporates a pretreatment test to monitor containment of the system (i.e. catheter body, supply lumen, guidewire lumen, balloons) prior to any treatment procedures. In the case of a breach in the system, the fluid shutoff will inhibit any flow of cryogenic fluid into the catheter. The pre-treatment test may be effected by introducing a pulse of gas, typically nitrous oxide, into a balloon with a supply lumen and exhausting the gas. Containment of the supply lumen, balloon, guidewire lumen, and catheter body are monitored by measuring a gas pulse pressure. Flow of cryogenic fluid is inhibited into the balloon if the measured pressure is below a threshold pressure.
In still another aspect of the present invention, methods for enhancing cryogenic cooling fluid flow rates in a cryotherapy system are provided. The method comprises introducing a cryogenic cooling fluid into a balloon with a supply lumen. The balloon is flooded so that at least some of the cooling fluid is exhausted in the balloon and at least some of the cooling fluid overflows into an exhaust lumen. The supply lumen and cryogenic fluid therein are cooled so as to enhance a flow rate of the cryogenic cooling fluid. Enhanced flow rates achieved from flooding the cryotherapy balloon also allow the supply lumen diameter to be reduced to a range from about 0.004 inches to about 0.012 inches. Moreover, the cryotherapy system may be less dependent on fluid canister pressure as enhanced flow rates compensate for lower cryogenic cooling fluid canister pressurizations at a range from about 850 psi to about 600 psi.
A further understanding of the nature and advantages of the present invention will become apparent by reference to the remaining portions of the specification and drawings.